Chaperonin Abundance Enhances Bacterial Fitness

Abstract

The ability of chaperonins to buffer mutations that affect protein folding pathways suggests that their abundance should be evolutionarily advantageous. Here, we investigate the effect of chaperonin overproduction on cellular fitness in Escherichia coli. We demonstrate that chaperonin abundance confers 1) an ability to tolerate higher temperatures, 2) improved cellular fitness, and 3) enhanced folding of metabolic enzymes, which is expected to lead to enhanced energy harvesting potential.

Mycobacterial chaperonins in cellular proteostasis: Evidence for chaperone function of Cpn60.1 and Cpn60.2‐mediated protein folding

“…We found that the amount of GroEL produced due to the leakiness of the P trc promoter (Figure S2 d) was sufficient to support colony growth. Furthermore, we found high‐level overexpression of groEL (Figure 2b and Figure S5 ), and co‐overexpression of groEL and Mtbcpn60.2 (Figure 2b ) to be lethal, which is likely due to the fitness costs associated with chaperonin overproduction (Kumar et al, 2021 ; Sabater‐Muñoz et al, 2015 ).…”

“…For optimal fitness, cells regulate chaperonin levels to maintain an economical balance in the rates of protein synthesis and folding (Santra et al, 2017 ). Excess chaperonins are likely to reduce cellular fitness by holding essential proteins through prolonged, non‐specific and often non‐productive binding (Badcoe et al, 1991 ; Kumar et al, 2021 ; Kumar & Mande, 2011 ), thereby reducing their availability for cellular housekeeping functions. Furthermore, chaperonin overproduction was previously shown to have high energetic (Sabater‐Muñoz et al, 2015 ) and metabolic (Kumar et al, 2021 ) costs and may have additional fitness costs associated with translational overload and reduced overall cellular protein synthesis capacity (Dong et al, 1995 ).…”

Proteostasis is a master modulator of molecular evolution in bacteria

“…PQC can also enhance adaptation to specific environmental stressors relevant to industrial applications; for example, extended thermal tolerance was achieved by GroEL overexpression. The GL-Ht strain overexpressing GroEL displayed elevated bacterial fitness and grew in a wide range of temperatures as expected due to the structure stabilization that chaperones provide [25]. GroEL can also enhance adaptation to hot environments when increased salt concentrations (such as ammonium sulfate) stabilize the chaperone under thermophilic conditions [134].…”

“…Maintaining proteostasis by molecular chaperones has been observed as a fundamental principle across the three domains of life [25]. However, despite the absence of a universally conserved canonical chaperone across all domains of life, evidence still points to early evolution that may have occurred after diversification from the last universal common ancestor (LUCA) [1,26].…”